Clinical Study Evaluating the Safety and Efficacy of Roflumilast in Type 2 Diabetic Patients With Diabetic Neuropathy

Diabetic Neuropathies Clinical Trial

Official title:

Clinical Study Evaluating the Safety and Efficacy of Roflumilast in Type 2 Diabetic Patients With Diabetic Neuropathy

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05369793
• Other study ID #: 35420/4/22
• Status: Completed
• Phase: Phase 3
• Start date: August 1, 2022
• Est. completion date: October 10, 2023

Study information

• Verified date: November 2023
• Source: Tanta University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Evaluation of the side effects and efficacy of roflumilast on glycemic parameters, insulin resistance, oxidative and inflammatory markers in Type 2 diabetic patients with diabetic neuropathy.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 60
• Est. completion date: October 10, 2023
• Est. primary completion date: October 10, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 25 Years to 65 Years

Eligibility

Inclusion Criteria:

• Patients with a diagnosis of type 2 diabetes mellitus (T2DM).

• HbA1c at baseline: =7.5 % to 8.5 %.

• BMI between =26 and =35 kg/ m2.

• Established Diabetic neuropathy diagnosed by nerve conduction study (NCS).

Exclusion Criteria:

• Patients diagnosed with type 1 diabetes mellitus or diabetes secondary to pancreatitis or resection of the pancreas.

• Patients diagnosed with hemoglobinopathies, hemolytic anemia, or other diseases which interfere with HbA1c measurement.

• Thyroid disease, cardiovascular disease, peripheral vascular disease, coagulopathy, moderate to severe liver disease (bilirubin>1.5mg), or renal excretion =90ml/min.

• Patients on medications which can result in a change of weight (orlistat, metformin, clozapine, gabapentin) and patients on medications that can interfere with glucose or lipid metabolism (corticosteroids, non-selective ß-blockers, thiazides, etc.)

• Treatment with any diabetes medications other than glimepiride prior to intervention.

• Clinically significant cardiac abnormalities (diagnosed clinically, history, or by X-ray/ECG) that were not related to type 2 diabetes mellitus and that required further evaluation.

• Patients with morbid obesity (BMI = 40 kg/ m2).

• History or current diagnosis of major depressive disorders or other psychiatric disorders.

• Pregnant and breastfeeding women.

• Patients with any inflammatory diseases.

• Patients on cytochrome P450 inducers (e.g., rifampicin, phenobarbital, carbamazepine, phenytoin, etc.).

• Patients with Low vitamin B12 levels according to suggested normal values for T2DM patients over 60 years old (<400 pmol/L).

Related Conditions & MeSH terms

• Diabetic Neuropathies
• Peripheral Nervous System Diseases

Intervention

Drug:
• Alpha lipoic acid
Administration of alpha-lipoic acid 600mg plus vildagliptin/metformin combination (50/1000mg) orally once daily for 3 months.
• Roflumilast
Administration of 500 mcg plus vildagliptin/metformin combination(50/1000mg) orally once daily for 3 months.

Locations

Country	Name	City	State
Egypt	Asmaa Elshafey Elsharab	Tanta

Sponsors (1)

Lead Sponsor	Collaborator
Tanta University

Country where clinical trial is conducted

Egypt, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Assessment of changes in patients' quality of life	Using Diabetes Quality Of Life questionnaire (DQOL)	baseline and 3 months later
Other	Major adverse cardiovascular events (MACE)	Major adverse cardiovascular events (MACE) as non-fatal myocardial infarction (MI), non-fatal stroke, and cardiovascular death.	3 months
Primary	Change in fasting blood glucose	Using glucose oxidase method for assessment of blood glucose and subtracting pre-treatment from post-treatment values	baseline and 3 months later
Primary	Change in plasma insulin level	Subtracting pre-treatment from post-treatment values of plasma insulin	baseline and 3 months later
Primary	Change in HOMA-IR index	HOMA-IR will be calculated for all patients at baseline and 3 months later.	baseline and 3 months later
Primary	Change in HOMA-B index	HOMA-B will be calculated for all patients at baseline and 3 months later.	baseline and 3 months later.
Primary	Change in HbA1c	Subtracting pre-treatment from post-treatment values of HbA1C	baseline and 3 months later
Secondary	Changes in TNF-alfa serum level	Subtracting pre-treatment from post-treatment values of TNF-alfa.	baseline and 3 months later
Secondary	Changes in malondialdehyde serum level (MDA)	Subtracting pre-treatment from post-treatment values of MDA.	baseline and 3 months later
Secondary	Changes in neurotensin serum levels	Subtracting pre-treatment from post-treatment values of neurotensin serum levels.	baseline and 3 months later
Secondary	Ewing score	Subtracting pre-treatment from post-treatment changes in summation of the cardiac autonomic reflex tests (CARTs) including heart response to a deep breathing test, changes in immediate heart rate response to standing, and changes in blood pressure response to sustained handgrip testing.	baseline and 3 months later
Secondary	Changes of Michigan Neuropathy Screening Instrument	A 15-item questionnaire (MNSIQ) is used to assess deformation, infection, skin thickening of the skin's stratum corneum, and ulcers.; MNSIQ was designed to screen for diabetic neuropathy through questionnaires on 15 questions that are related to neuropathic symptoms (pain, temperature, and sensation). Two of 15 (number 4 and 10) are vascular symptoms and are excluded from the total score regardless of the results. If you answered 'No' to questions 7 and 13, you will get 1 point. In the end, scores ranging from 0 to 13 indicate that the higher the score, the more severe the neuropathic symptoms.	baseline and 3 months later
Secondary	Changes of Michigan Neuropathy Screening Instrument(MNSIE)	A foot test (MNSIE) is used to assess deformation, infection, skin thickening of the skin's stratum corneum, and ulcers.; MNSIE evaluates foot shape, foot ulceration, ankle reflex, sense of vibration of big toe, monofilament right and left. The score ranges from point 0 to 10, and when the score is above 2, it is diagnosed as neuropathy.	baseline and 3 months later
Secondary	Changes of Douleur Neuropathique-4 (DN4) questionnaire (DN4)	DN4 Neuropathic Pain Diagnostic Questionnaire which reflect positive symptoms for pain ( burning, painful cold, electric shocks, )	baseline and 3 months later